Center for Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.
J Virol. 2012 Jan;86(1):121-7. doi: 10.1128/JVI.06085-11. Epub 2011 Oct 19.
Oseltamivir-resistant H1N1 influenza viruses emerged in 2007 to 2008 and have subsequently circulated widely. However, prior to 2007 to 2008, viruses possessing the neuraminidase (NA) H274Y mutation, which confers oseltamivir resistance, generally had low growth capability. NA mutations that compensate for the deleterious effect of the NA H274Y mutation have since been identified. Given the importance of the functional balance between hemagglutinin (HA) and NA, we focused on amino acid changes in HA. Reverse genetic analysis showed that a mutation at residue 82, 141, or 189 of the HA protein promotes virus replication in the presence of the NA H274Y mutation. Our findings thus identify HA mutations that contributed to the replacement of the oseltamivir-sensitive viruses of 2007 to 2008.
2007 年至 2008 年出现了对奥司他韦耐药的 H1N1 流感病毒，并随后广泛传播。然而，在 2007 年至 2008 年之前，具有神经氨酸酶（NA）H274Y 突变的病毒通常生长能力较低。此后，已鉴定出可补偿 NA H274Y 突变有害影响的 NA 突变。鉴于血凝素（HA）和 NA 之间功能平衡的重要性，我们专注于 HA 中的氨基酸变化。反向遗传分析表明，HA 蛋白残基 82、141 或 189 处的突变促进了在存在 NA H274Y 突变的情况下病毒的复制。因此，我们的研究结果确定了有助于取代 2007 年至 2008 年对奥司他韦敏感的病毒的 HA 突变。
